Novel class of peptidomimetics, and cyclic peptidomimetics have become appealing targets for the design of therapeutic agents with increased pharmacological activities. Therapeutic potential and demand of opioid analgesics have initiated numerous amounts of scientific efforts, which have resulted in development of a number of new opioid analgesics and significant expansion of knowledge on the opioid pharmacology. Structurally diverse ligands are needed to aid in the study of the mechanisms of analgesic efficacy, addiction and tolerance, and may lead to effective new forms of analgesics or alternative treatments for drug abuse. Therefore, we propose an innovative design for the synthesis of new oligoheterocyclic peptidomimetics. All the proposed compounds will be screened internally in different assays for opioid activity in mu, delta, and kappa opioid receptors. PUBLIC HEALTH RELEVANCE: Opioid analgesics provide outstanding benefits for relief of severe pain. New opioid drugs and therapies with more desirable properties can be developed on the bases of accurate insight of the opioid ligand-receptor interaction and clear knowledge of the pharmacological behavior of opioid receptors and the associated proteins. Peptidomimetics are compounds which mimic the biological activity of peptides while offering the advantages of increased bioavailability, biostability, bioefficiency, and bioselectivity against the natural biological target of the parent peptide. Examples of peptidomimetics have been isolated as natural products, synthesized as libraries from novel subunits, aiming to improve receptor affinity and selectivity. They offer challenging synthetic targets and are increasingly important medicinal agents and biological probes. We propose the design and the synthesis of unique oligoheterocyclic peptidomimetics and cyclic peptidomimetics. All the proposed compounds will be screened internally in different assays for opioid activity in mu, delta, and kappa opioid receptors.